Decreased Homocysteine Levels Research Articles

Prospective Observational Study Of Hyperhomocysteinemia In Patients With Recurrent Pregnancy Loss In Teaching Hospital

Background: Spontaneous pregnancy loss can be physically and emotionally taxing for couples, especially when faced with recurrent losses. Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period . RPL is also defined by two or more failed consecutive pregnancies. It is estimated that fewer than 5% of women will experience two consecutive miscarriages and only 1% experience three or more. At present, there exists a small number of accepted etiologies for RPL. Most of the diagnosed etiologies include endocrine abnormalities, autoimmune disorders, uterine anomalies, and genetic factors. After evaluation for these causes, approximately half of all cases will still remain unexplained. Hence the present study was taken up to investigate the association between hyperhomocysteinemia and recurrent pregnancy loss, evaluating prevalence, potential mechanisms and implications for management. Materials and Methods: The prospective observational study was conducted on 50 patients in the Department of OBG in Dr. B. R. Ambedkar Medical College and Hospital for a period of 18 months. Prior to the initiation of the study, Ethical and Research Committee clearance was obtained from Institutional Ethical Committee. Results: The majority of participants in both groups were aged 35 to 40 years (32.35% in Group A and 37.5% in Group B).Statistically significant differences were observed between the groups regarding hypertensive disorders of pregnancy, co-morbidities, adverse pregnancy outcomes, the nature of abortion (primary vs. secondary), fetal outcomes, APGAR scores at 1 and 5 minutes, neonatal birth weight, and NICU admissions, with p-values of 0.001 across these measures.Group B (with hyperhomocysteinemia) showed higher instances of hypertensive disorders, co-morbidities, adverse pregnancy and fetal outcomes, abnormal APGAR scores at 1 and 5 minutes, lower neonatal birth weight, and NICU admissions.The mean homocysteine levels were 13.28 ± 1.8 µmol/L in Group A and 73.98 ± 5.1 µmol/L in Group B, with a highly significant difference (p: 0.0001).Most subjects in Group B had intermediately severe hyperhomocysteinemia (50%), with 37.5% experiencing moderately severe hyperhomocysteinemia and 12.5% with severe hyperhomocysteinemia. All abortions in Group A were primary, whereas Group B had 60% primary and 40% secondary abortions. Conclusion: Hyperhomocysteinemia is a risk factor for recurrent pregnancy loss. About 1 in 3 patients of RPL have hyperhomocysteinemia and therefore as a routine workup for RPL serum homocysteine measurement should also be included. Treatment of hyperhomocysteinemia with folic acid and vitamin B12 decreases homocysteine levels significantly.

Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer

Hydrogen sulfide (H₂S), a metabolite of the transsulfuration pathway, has been implicated in ferroptosis, a unique form of cell death caused by lipid peroxidation. While the exact mechanisms controlling ferroptosis remain unclear, our study reveals that H₂S sensitizes human non-small cell lung cancer (NSCLC) cells to this process, particularly when cysteine levels are low. Combining H₂S with cystine depletion significantly enhances the effectiveness of ferroptosis-based cancer therapy. Mechanistically, H₂S persulfidates the 195th cysteine on S-adenosyl homocysteine hydrolase (SAHH), reducing its enzymatic activity. This leads to decreased homocysteine levels, subsequently lowering cysteine and glutathione concentrations under cystine depletion conditions. These changes ultimately increase the vulnerability of NSCLC cells to ferroptosis. Our findings establish H₂S as a key regulator of homocysteine metabolism and a critical factor in determining NSCLC cell susceptibility to ferroptosis. These results highlight the potential of H₂S-based therapies to improve the efficacy of ferroptosis-targeted cancer treatments for NSCLC.

B vitamins and homocysteine in cancer patients with solid malignancies before chemotherapy administration

Recently, the role of vitamin imbalance in carcinogenesis has been actively discussed. Studies aimed at assessing their role in the processes of cancer development are various, and the evaluation of the initial level of vitamins is relevant when planning antitumor therapy.Objective. To determine the state of the initial level of B vitamins and homocysteine before chemotherapy in patients of different oncologic profile.Material sand Methods. The level of vitamins B1, B6, B9, active form of B12* and homocysteine in fresh frozen plasma was determined by enzyme[1]linked immunosorbent assay (ELISA) using test systems in 66 patients with verified malignant neoplasms before chemotherapy. The study included 66 patients: women n=40 and men n=26, with cancer: gastric n=12, colorectal cancer n=21, cancer lung n=11, cancer pelvic organs n=22.Results. According to the results of the study the increase in the level of holotranscobalamin (Holo-TC) and decrease in homocysteine in comparison with reference values was observed in 100% of cases. Significant difference was found only for B1: reliable differences between patients with colorectal cancer and with pelvic cancer (in the latter the mean value of B1 levels was 2.4 times higher at p = 0.0425). According to the results of correlation analysis, a weak correlation between B12 and B9 was determined. When comparing the levels of vitamin B12 and homocysteine in patients after surgical treatment and without it, no significant differences were found.Conclusion. Increased Holo-TC levels and decreased homocysteine levels by ELISA are characteristic of all varieties of solid cancer, independent of sex, age, stage and previous surgical intervention. A relative decrease in vitamin B1 is characteristic of colorectal cancer

Elevated homocysteine is negatively correlated with plasma cystathionine β-synthase activity in givosiran-treated patients.

Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran-treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B6, a cofactor for CBS, in four patients during the trial, plasma CBS activity was found to increase, mirroring a corresponding decrease in homocysteine levels. These results support the hypothesis that elevated homocysteine levels following givosiran treatment result from a reduction of CBS activity and that vitamin B6 supplementation lowers homocysteine levels by increasing CBS activity.

Fortified foods with methylated forms of B vitamin for the prevention of hyperhomocysteinemia

Aim. To study the relationship between blood homocysteine levels and genetic and epigenetic factors and assess the possibility of correcting homocysteine levels using products enriched with methylated forms of B vitamin.Material and methods. The study included 20 people (6 men and 14 women) aged 24-67 years (mean age — 41,5 years). Muscleto-fat ratio was determined by bioelectrical impedance analysis. The plasma concentration of homocysteine was measured using an immunochemistry analyser. Polymorphism analysis of folate cycle genes was performed using polymerase chain reaction. Statistical processing of the material, training and data prediction was performed using artificial neural networks (ANNs). Homocysteine levels before a 3-month consumption of fortified products are presented as Hc1, after — Hc2.Results. The blood level of homocysteine before taking fortified fruitberry bars varied from 6,5 to 24,2 µmol/l, averaging 12,45±2,9 µmol/l. After 3 months of use, the blood homocysteine level decreased to the range of 7,1-18 µmol/l and, on average, amounted to 10,87±2,6 µmol/l (p=0,028). Hyperhomocysteinemia was detected in two women (19,7 and 24,2 µmol/l) and one man (17,1 µmol/l). After consuming fruitberry bars, a significant decrease in blood homocysteine levels was observed from 19,7 to 14,3 µmol/l, from 24,2 to 14,1 µmol/l and from 17,1 to 15,5 µmol/l, respectively. A significant average correlation was revealed between Hc1 and Hc2 (r=0,579; p<1×10-5). Correlations were noted between blood homocysteine levels and body mass index, as well as responses about elevated blood glucose levels and the frequency of desire to reduce body weight (p<6,74×10-5).Conclusion. The results demonstrate a significant decrease in blood homocysteine in all participants when taking food products fortified with methylated forms of B vitamin (p=0,028). Individuals adhering to dietary restrictions showed a more pronounced decrease in homocysteine levels (p<6,74×10-5).

Impact of vitamin B12 on the reproductive health of women with sickle cell disease: a narrative review.

Sickle cell disease (SCD) poses an increased risk of infertility, pregnancy complications and maternal and perinatal mortality among women of reproductive age. This risk is particularly higher for women in sub-Saharan Africa, where the disease burden is highest and access to comprehensive health care is limited, as well as in other countries with a high SCD prevalence due to migration. Disease modifying treatments for SCD could directly and indirectly harm the ovaries, potentially compromising quality and quantity of existing oocytes. Therefore, it is essential to explore alternative interventions, such as nutritional modifications that are less harmful and cost-effective in order to improve reproductive outcomes, and enhance the overall well-being of both mother and child in this population. Maintaining optimal levels of B12 may possibly provide benefits to the ovaries and pregnancy by decreasing homocysteine levels, increasing nitric oxide (NO) bioavailability, and promoting antioxidant and anti-inflammatory activities. Individuals living with SCD are more susceptible to vitamin B12 (B12) deficiency. However, there is a lack of clinical data investigating the relationship between systemic levels of B12, its supplementation, and reproductive outcome measures in SCD women. Therefore, this review aims to examine the current evidence regarding the impact of SCD on female reproductive health and the role of B12 in the reproductive biology of women living with SCD.

Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition.

Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of the metabolic alterations that occur in different organs in diabetes and in response to SGLT2i. In vivo metabolic labeling with 13C-glucose in normoglycemic and diabetic mice treated with or without dapagliflozin, followed by metabolomics and metabolic flux analyses, showed that, in diabetes, glycolysis and glucose oxidation are impaired in the kidney, liver, and heart. Treatment with dapagliflozin failed to rescue glycolysis. SGLT2 inhibition increased glucose oxidation in all organs; in the kidney, this was associated with modulation of the redox state. Diabetes was associated with altered methionine cycle metabolism, evident by decreased betaine and methionine levels, whereas treatment with SGLT2i increased hepatic betaine along with decreased homocysteine levels. mTORC1 activity was inhibited by SGLT2i along with stimulation of AMPK in both normoglycemic and diabetic animals, possibly explaining the protective effects against kidney, liver, and heart diseases. Collectively, our findings suggest that SGLT2i induces metabolic reprogramming orchestrated by AMPK-mTORC1 signaling with common and distinct effects in various tissues, with implications for diabetes and aging.

Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.

The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). Retrospective chart review. Tertiary academic medical center. Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. Two hundred sixty-onepatients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.

Dynamics of homocysteine level in patients with osteoporotic fracture

The research was carried out in order to investigate the blood serum level of homocysteine (HCY) which is involved in bone metabolism and has prognostic significance in the monitoring of the regenerative processes in osteoporosis and osteoporotic fractures. The study was carried out on patients 45-83 years old divided into 3 groups: group I – 14 patients with osteoporosis confirmed by densitometry or X-ray examination­, group II – 15 patients with non-osteoporosis fractures, group III – 25 patients with osteoporotic fractures. The control group consisted of practically healthy 14 people. In patients with various fractures osteosynthesis with Ilizarov apparatus or with metal plates was performed. After the operation, the patients were treated in an inpatient setting for a week, then sent for outpatient treatment and prescribed calcium and vitamin D supplements to accelerate the bone regeneration process. A blood sample was taken at 3 stages to monitor the dynamics of HCY level by Elisa test: on the 1st day before treatment, on the 10th day of treatment and 1 month after it. The results showed that on the 1st day before the treatment HCY concentration was statistically increased 2.7 times in group I, 5.6 times in group II, and 6.5 times in group III compared to the control group. In the month of recovery, a significant decrease in HCY level was observed in all treated groups but it still remained higher than in the control indicating the need to recommend additional therapeutic prescriptions. Keywords: level of homocysteine, osteoporosis, osteoporotic fractures

Investigation into the Properties of L-5-Methyltetrahydrofolate and Seal Oil as a Potential Atherosclerosis Intervention in Rats.

Atherosclerosis is a chronic inflammatory disease that leads to tissue ischemia. As the biologically active form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF) can improve endothelial function. And Seal oil plays a beneficial role in the progression of atherosclerosis. The study aims to evaluate beneficial effects of L-5-MTHF alone or in combination with Seal oil on atherosclerosis. Seventy-two male Wistar rats were randomly divided into 6 groups: control (normal diet), atherosclerosis (high-fat diet), folic acid (high-fat+3 mg/kg folic acid), low-dose L-5-MTHF (high-fat+3 mg/kg L-5-MTHF), low-dose L-5-MTHF+Seal oil (high-fat+3 mg/kg L-5-MTHF+0.5 g/kg Seal oil), high-dose L-5-MTHF (high-fat+10 mg/kg L-5-MTHF). After 13 wk, rats were sacrificed. Rats exhibiting atherosclerosis had dyslipidemia and serious aortic lesions. Supplementation with low-dose L-5-MTHF+Seal oil or use of high-dose L-5-MTHF increased serum folate concentrations, decreased homocysteine levels, improved the serum lipid profile, up-regulated expression of NO and NOS, enhancement of the antioxidant properties of GSH-Px activity and reduction in the concentration of MDA, levels of Olr1 and RelA mRNA decreased in aortic tissues, and expression of inflammatory factors, TNF-α, IL-6, IL-1β and endothelial cell injury factors ET-1 and sICAM-1, were also down-regulated. In addition, HD-L-5-MTHF increased the antioxidant activity of serum SOD. We conclude that L-5-MTHF has obvious anti-inflammatory and antioxidant effects on diseased blood vessels. The intervention of L-5-MTHF alone or in combination with Seal oil can improve atherosclerosis in rats and reduce the occurrence of aortic lesions. The anti-atherosclerotic mechanism may be related to down-regulation of Olr1 and RelA expression.

Early supplementation of folate and vitamin B12 improves insulin resistance in intrauterine growth retardation rats.

Insulin sensitivity is changed during the neonatal period in small for gestational age (SGA) infants. Yet, the interventional strategies are still limited. We aimed to investigate the effects of supplementation with high folate and vitamin B12 diets in the early postnatal period on the changes in insulin sensitivity in an intrauterine growth retardation (IUGR) rat model. IUGR rat model was established by both low-protein diet feeding and daily diet restriction. High folate and vitamin B12 diet was supplied in IUGR as nutritional interventional group (IUGR-I), otherwise, the non-intervened IUGR group (IUGR-NI). In this study, male rats were studied in order to avoid hormonal and gender influence. At 21, 60 and 120 days, fasting plasma glucose, insulin, triglyceride, cholesterol, and homocysteine levels were measured among the control, IUGR-I, and IUGR-NI groups. Pearson analysis was used to evaluate the correlation between homocysteine and fasting blood glucose, insulin, HOMA-IR, triglyceride, and cholesterol levels. We established IUGR rat model by both low protein and restricted diet feeding during pregnancy and the incidence of IUGR pups was 93.33%. There was no difference in fasting glucose, insulin, HOMA-IR, triglyceride and cholesterol levels between the control, the IUGR-NI and the IUGR-I group at day 21. At day 60, insulin, HOMA-IR and triglyceride levels in the IUGR-I group were remarkably lower than those in the IUGR-NI group, but still higher than those in the control group (F=38.34, P=0.02; F=49.48, P=0.02; F=17.93, P<0.001, respectively). At day 120, glucose, insulin, HOMA-IR and Hcy levels in the IUGR-I group were obviously lower than those in the IUGR-NI group, although still higher than those in the control group (F=21.60, P<0.001; F=164.46, P<0.001; F=75.15, P<0.001; F=35.46, P<0.001, respectively). There were no significant differences in triglyceride and cholesterol levels between the IUGR-I group and the control group at day 120. At 120-day, homocysteine in IUGR-I group was highly positively correlated with fasting glucose and HOMA-IR (r=0.863, P=0.006; r=0.725, P=0.042, respectively); Only homocysteine was positively correlated with fasting glucose in IUGR-NI group (r=0.721, P=0.044). Early supplementation of folate and vitamin B12 improved insulin resistance and lipid levels in IUGR rats to some extent, along with decreasing homocysteine levels, but not enough to completely repair glucose and lipid metabolism.

Effect of zinc supplementation on circulating concentrations of homocysteine, vitamin B12, and folate in a postmenopausal population

IntroductionThe decrease in estrogen levels associated with menopause increases the risk of deficiencies of key micronutrients such as zinc and of disturbances in methylation cycle-related markers. The present study assesses the effect of 8-week Zn supplementation upon circulating concentrations of Hcy, B12, and Fol levels in a population of postmenopausal women. MethodsFifty-one postmenopausal women aged between 44 and 76 years took part in the study. Two randomized groups (placebo and zinc [50 mg/day]) were treated during 8 weeks. Nutrient intake was assessed based on the 72-hour recall method. Zinc was analyzed by flame atomic absorption spectrophotometry. Clinical-nutritional parameters were determined by enzyme immunoassay techniques. ResultsFolate levels increased significantly (p < 0.05) in the zinc group on comparing the baseline versus follow-up values. Homocysteine decreased in the inter-group analysis (p < 0.05) after the intervention. Furthermore, higher folate (r = −0.632; p = 0.005) and vitamin B12 (r = −0.512; p = 0.030) levels were correlated to low homocysteine levels in the zinc group after the intervention, although the zinc intervention had the same effect on B12 levels in both groups. ConclusionZinc supplementation enhanced circulating folate and homocysteine by improving the folate values in the zinc-supplemented group and decreasing homocysteine levels inter-groups. Further studies involving larger samples and optimizing the doses and intervention period are needed to reinforce our main findings.

The effect of vitamin D and homocysteine on DNA regulation of beta-amyloid.

At the cellular level the human body is a bioactive reactor, many symbiotic biochemical reactions are taking place at the DNA level to maintain the integrity of the neurons. 373 patients presented for memory evaluation in the last 5 years. A Montreal Cognitive Assessment (MoCA) was given as a standard cognitive test for dementia evaluation and part of memory blood panel serum vitamin D, vitamin B12, folate, and homocysteine were done. Results of the serum blood tests were correlated with MoCA scores. MoCA scoring: Normal (30-26), Mild (25-21), Moderate (20-16), Severe (<16). Regression statistical analysis showed that patients' homocysteine levels had linear relation to their MoCA scores (t = -3.81, df = 233, p < 0.001). For every 1 uM increase in homocysteine levels, there was a 0.21997 decrease in MoCA scores, on average. Vitamin D levels had linear relation with their Homocysteine levels (t = -2.40, df = 302, p = 0.017). For every 1 ng/mL increase in vitamin D, there was a 0.04277 uM decrease in homocysteine, on average. Similar relation was between homocysteine levels and vitamin B12 levels (t = -3.39, df = 292, p < 0.001). For every 1 pg/mL increase in vitamin B12 there was a 0.004043 uM decrease in homocysteine levels, on average. Lastly, folate levels showed linear relation with homocysteine levels (t = -3.70, df = 250, p < 0.001). For every 1 ng/mL increase in folate, there was a 0.25375 uM decrease in homocysteine levels. At neuronal level, this complex biochemical activity is regulated by active DNA through demethylation and inactive DNA by methylation, with many cofactors playing a major role. In the methionine cycle, homocysteine is methylated to form methionine, a precursor to SAMe, which will ultimately allow for the transfer of a methyl group to a DNA regulation of Beta-Amyloid (Fuso, et. al 2006) is indirect evidence of linear correlation of this clinical lab value with MoCA Scores. This clinical study provides indirect evidence of the role of homocysteine and vitamin D in DNA regulation, activation, and the neuroprotective effect of homocysteine metabolism.

Effective Nutraceuticals on Age-Associated Cognitive Decline: A Systematic Review

Abstract Objectives The prevalence of neurodegenerative disorders such as dementia is positively correlated to aging. As there is insufficient evidence for the medicinal remedies of dementia, focusing on prevention strategies to use nutraceuticals could provide positive results. Therefore, this systematic review aimed to evaluate the effect of various nutraceuticals on age-associated cognitive decline. Methods Literature was searched using PubMed, EMBASE, Cochrane, and PsycINFO databases with the search terms being nutraceuticals in cognitive dysfunction. The literature was limited to human studies, randomized controlled trials, and a single material. Selection of literature, evaluation of the risk of bias, and assessment of the quality of evidence was conducted independently by two reviewers. Results We finally included 17 studies of literature after excluding the risk of bias ‘high.’ The evidence was rated ‘high’ quality for both omega-3 fatty acids and vitamin Bs. Other materials, including vitamins D &amp; E, anserine/carnosine, and chromium were identified as ‘moderate’ quality. Omega-3 fatty acids (0.48–2.2 g of DHA and 203–720 mg of EPA) relieved cognitive decline and amyloid β related proteins in participants with mild cognitive impairment. However, the cognitive decline did not have an effect on dementia patients. Vitamin B (25–500 µg of B12 and 20 mg of B6) group exhibited decreased homocysteine levels, followed by enhanced cognitive function. However, vitamin D &amp; E, anserine/carnosine, and chromium showed a shred of limited evidence owing to limited studies. Conclusions This study suggests that omega-3 fatty acids and vitamin B have protective effects against age-associated cognitive decline. Funding Sources This research was funded by Ottogi, grant number HY-201900000670003.

Impact of supplementation with vitamins B6 , B12 , and/or folic acid on the reduction of homocysteine levels in patients with mild cognitive impairment: A systematic review.

Hyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B12 , B6 , and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B6, B12 , and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B6 , B12 , and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B12 , and four vitamin B6 . Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12 , and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B6, B12 , and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.

POS0383 EFFECTS OF TOFACITINIB THERAPY ON ARGININE AND METHIONINE METABOLITES IN ASSOCIATION WITH VASCULAR PATHOPHYSIOLOGY IN RHEUMATOID ARTHRITIS: A METABOLOMIC APPROACH

Background:Rheumatoid arthritis (RA) has been associated with increased cardiovascular (CV) risk and metabolic changes.Objectives:We wished to determine how the Janus kinase (JAK) inhibitor tofacitinib influences vascular pathophysiology and metabolites of the arginine and methionine-homocysteine pathways.Methods:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib and evaluated at baseline and after 6 and 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels.Results:Twenty-six patients completed the study. Tofacitinib treatment maintained FMD and PWV. Ten mg bid tofacitinib significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. Tofacitinib transiently increased L-citrulline and L-NMMA and decreased homocysteine levels after 12 months. Based on L-citrulline, L-ornithine, ADMA and SDMA levels, L-arginine remained highly available for endothelial NO production. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with aCCP. Regarding vascular pathophysiology, only PWV and methionine correlated with each other after 12 months.Conclusion:Tofacitinib suppressed systemic inflammation in RA yielding stabilization of vascular function. It may exert CV protective effects in RA, at least in part, by shifting L-arginine metabolism to high arginine availability and decreasing homocysteine levels.Acknowledgements:This research was supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program ’(Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00015 (Z.S.) and by the WI188341 investigator-initiated research (IIR) grant obtained from Pfizer US (Z.S.).Disclosure of Interests:Boglárka Soós: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Edit Végh: None declared, Szilvia Szamosi Speakers bureau: Roche, Zsófia Pethö: None declared, Katalin Gulyás: None declared, György Kerekes: None declared, Éva Szekanecz: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, Novartis, Gabriella Szücs Speakers bureau: Actelion, Roche, Sager, Boehringer, Consultant of: Boehringer, Actelion, Sager, Uwe Christians: None declared, Jelena Klawitter: None declared, Tamas Seres: None declared, Zoltán Szekanecz Speakers bureau: Pfizer, Abbvie, Roche, Lilly, Novartis, Boehringer, Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: Pfizer

Alimentação como fator de proteção da doença de Alzheimer

A doença de Alzheimer (DA) caracteriza-se como uma síndrome neurodegenerativa que leva à perda das funções cognitivas e ocasiona comprometimento progressivo das atividades do dia-a-dia. Estudos tem demonstrado que a alimentação pode ter efeito neurológico protetor e redução do risco de desenvolver a DA. O objetivo desse estudo foi apresentar os principais nutrientes envolvidos na proteção da DA. Os principais nutrientes associados à prevenção da DA identificados nesse estudo são as vitaminas do complexo B, vitamina C, D e E, ômega 3 e selênio. Os mecanismos de proteção destes nutrientes à demência e ao retardo do declínio cognitivo estão associados ao seu poder antioxidante, papel no funcionamento dos neurotransmissores, diminuição dos níveis de homocisteína entre outros. Observou-se a importância da intervenção nutricional precoce no manejo da DA, o acompanhamento de portadores de DA com equipe multidiciplimar, bem como a utilização de métodos específicos de diagnóstico nutricional com o objetivo de prevenir os efeitos da DA.

Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial\xa0(Citrus study)

PurposeTo assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals.MethodsIn a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose–response studies were performed at baseline and after 12 weeks.ResultsA single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes related to hypertension (PTX3, NLRP3, NPSR1 and NAMPT) were differentially expressed in peripheral blood mononuclear cells (P < 0.05).ConclusionHesperidin in OJ reduces SBP and PP after sustained consumption, and after a single dose, the chronic consumption of EOJ enhances its postprandial effect. Decreases in systemic and transcriptomic biomarkers were concomitant with BP and PP changes. EOJ could be a useful co-adjuvant tool for BP and PP management in pre- and stage-1 hypertensive individuals.

The Elderly-Nutrient Rich Food Score Is Associated With Biochemical Markers of Nutritional Status in European Older Adults.

Background: In order to prevent age-related degenerative diseases in the aging population, their diets should be nutrient dense. For this purpose, the Elderly-Nutrient rich food (E-NRF7.3) score has been developed to assess nutrient density of diets by capturing dietary reference values for older adults. To demonstrate its practical importance such score should be validated against markers of nutritional status and health.Objective: The objective of this study was to examine the association between the E-NRF7.3 score and markers of nutritional status and inflammation.Design: This study was carried out in a sample of the NU-AGE study including 242 Dutch and 210 Polish men and women, aged 65–79 years. Dietary intake was assessed by means of 7-day food records and structured questionnaires collected data on supplement use, lifestyle, and socio-economic information. Baseline measurements included anthropometrics, physical and cognitive function tests, and a fasting venipuncture. E-NRF7.3 scores were calculated to estimate nutrient density of foods and the diet. Associations between the E-NRF7.3 scores and micronutrient status of vitamin D, folate, vitamin B12, homocysteine, and c-reactive protein (CRP) were examined using linear regression analysis while adjusting for confounders.Results: Each one unit increase in E-NRF7.3 score was associated with a 2.2% increase in serum folate in Dutch and 1.6% increase in Polish participants in the fully adjusted models (both p < 0.01). Each one unit increase in E-NRF7.3 was significantly associated with a 1.5% decrease in homocysteine levels in Dutch participants (p < 0.01), whereas, a 0.9% increase in vitamin B12 levels was observed in Polish participants only (p < 0.01). Higher E-NRF7.3 scores were not associated with vitamin D or CRP levels. Adjustment for potential confounders did not substantially alter these results.Discussion: The E-NRF7.3 was developed to reflect dietary intake of relevant nutrients for older adults. Its association with markers of nutritional status could be confirmed for folate (both populations), vitamin B12 (Poland only), and homocysteine (the Netherlands only). There was no association with vitamin D and CRP. To further demonstrate its validity and practical implication, future studies should include a wider range of nutritional status makers, health outcomes, and inflammation markers.

Fish oil plus wheat germ oil have no prominent effect on homocysteine levels and nutritional indices in hemodialysis patients.

Background: Elevated homocysteine levels and malnutrition are frequently detected in hemodialysis patients and are believed to exacerbate cardiovascular comorbidities. Omega-3 fatty acids have been postulated to lower homocysteine levels by up-regulating metabolic enzymes and improving substrate availability for homocysteine degradation. Additionally, it has been suggested that prevention of folate depletion by vitamin E consumption decreases homocysteine levels. However, data on the effect of omega-3 fatty acids and/or vitamin E on homocysteine levels and nutritional status have been inconclusive. Therefore, this study was planned to examine the effect of combined supplementation of fish oil, as a source of omega-3 fatty acids, with wheat germ oil, as a source of vitamin E, on homocysteine and nutritional indices in hemodialysis patients. Methods: This study was a randomized, double-blind, placebo-controlled trial. Forty-six hemodialysis patients were randomly assigned to two equally-sized groups; a supplemented group who received 3000 mg/day of fish oil [1053 mg omega-3 fatty acids] plus 300 mg/day of wheat germ oil [0.765 mg vitamin E], and a matched placebo group who received placebo capsules for 4 months. Serum homocysteine and different nutritional indices were measured before and after the intervention. Results: Twenty patients in each group completed the study. At the end of the study, there were no significant changes in homocysteine levels and in the nutritional indices neither in the supplemented nor in the placebo-control groups (p>0.05). Conclusions: Fish oil and wheat germ oil combination did not produce significant effects on serum homocysteine levels and nutritional indices of hemodialysis patients.